The AIDS epidemic is a multitude of diverse epidemics. The epidemic throughout much of the Americas is concentrated primarily in men who have sex with men (MSM). Unlike all other risk groups in the US, HIV infection rates among MSM in the US have been climbing since the early 1990s. Epidemiologic research throughout much of Central and South America confirm these trends in MSM throughout these regions. Despite recent setbacks in the HIV vaccine and microbicide fields, a number of promising biomedical and behavioral HIV prevention strategies are currently under evaluation, with results expected in the next few years. These include pre-exposure prophylaxis (PrEP) (the use of antiretroviral medication for high-risk HIV uninfected person); male circumcision (highly effective for heterosexuals, not yet evaluated for MSM); treatment of stimulant use (many new promising pharmacologic agents being tested for methamphetamine and cocaine use); strategies to increase uptake and frequency of HIV testing (as people unaware of their infection appear to be driving the epidemic); prevention for HIV positive sex partners, including antiretroviral therapy (ART) and possible herpes (HSV2) suppressive therapy (for those who are HIV/HSV2 co-infected), and a variety of behavioral approaches, including interventions to improve adherence to medical regimens, minimize risk compensation, and help individuals with HIV disclosure and make sound decisions about serosorting. This application brings together a team of leading epidemiologists, biostatisticians, mathematical modelers, behavioral scientists, clinical scientists, and community members to build a comprehensive Prevention Umbrella for MSM in the Americas (the PUMA Project). The specific aims are to 1) conduct systematic reviews, conduct epidemiologic analysis and modeling to guide the selection of individual and partnership-level HIV prevention interventions and the appropriate target populations for MSM in the Americas; 2) build the individual components of a menu-driven HIV prevention package and design an individual-level randomized controlled trial to rigorously evaluate its impact on HIV seroincidence in high-risk HIV-uninfected MSM; and 3) determine the feasibility and acceptability of the individual and combined components of the proposed package of prevention package. The long term goal of this research is to develop an optimal HIV prevention package for MSM in the Americas and to design a clinical study to evaluate the safety and efficacy of this promising combination of interventions. This research will build a package of different medical and counseling approaches that, in combination, are likely to have the biggest impact on stopping new HIV infections in men who have sex with men in North and South America. At the end of this 4-year project, we will have a full package of prevention approaches that will be ready to be tested in 4000-5000 men in North and South America, to see if we can drive down infection rates in this population.